scholarly journals The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

Regeneration ◽  
2018 ◽  
Vol 5 (1) ◽  
pp. 3-25 ◽  
Author(s):  
Laura Florez-Sampedro ◽  
Shanshan Song ◽  
Barbro N. Melgert
Keyword(s):  
Immune Cells ◽  
Wound Repair

scholarly journals Skin stem cells orchestrate de novo generation of extrathymic regulatory T cells to establish a temporary protective niche during wound healing

2021 ◽  
Author(s):  
Cynthia Truong ◽  
Weijie Guo ◽  
Liberty Woodside ◽  
Audrey Gang ◽  
Peter Savage ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
T Cells ◽  
Immune Cells ◽  
Wound Repair ◽  
Adult Stem Cells ◽  
De Novo ◽  
Treg Cells ◽  
Adaptation Capacity ◽  
Hair Follicle Stem Cells

Adult stem cells reside in various tissues to govern homeostasis and repair damage. During wound healing, these stem cells must be mobilized to enter the center of the injury where they are exposed to many inflammatory immune cells infiltrating the wounded tissue. While these immune cells are indispensable for preventing infections and clearing dead cells, they can also create a harsh inflammatory environment which could potentially damage the stem cells and prevent their self-renewal and differentiation. Here, using a model of cutaneous wound healing in which hair follicle stem cells (HFSCs) repair the wound, we show that, upon migrating into the wound, skin stem cells acquire a strong immune modulatory capacity which allows them to sculpt a temporary immune suppressive niche for self-protection. We reveal that the HFSCs in the wound bed orchestrate extrathymic differentiation of regulatory T (Treg) cells by providing co-stimulation to the wound-infiltrating CD4 effector T cells. In this way, Treg cells can be generated de novo in close proximity to and can intimately protect HFSCs from the collateral damage inflicted by inflammatory neutrophils. This study uncovered a striking inflammatory adaptation capacity unique to adult tissue stem cells which allows them to shape their own immune suppressive niche during wound repair.

scholarly journals Intestinal Mucosal Wound Healing and Barrier Integrity in IBD–Crosstalk and Trafficking of Cellular Players

2021 ◽  
Vol 8 ◽  
Author(s):  
Katrin Sommer ◽  
Maximilian Wiendl ◽  
Tanja M. Müller ◽  
Karin Heidbreder ◽  
Caroline Voskens ◽  
...  
Keyword(s):  
Wound Healing ◽  
Immune Cells ◽  
Wound Repair ◽  
Intestinal Inflammation ◽  
Healing Process ◽  
Epithelial Barrier ◽  
Wound Healing Process ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Mucosal Wound

The intestinal epithelial barrier is carrying out two major functions: restricting the entry of potentially harmful substances while on the other hand allowing the selective passage of nutrients. Thus, an intact epithelial barrier is vital to preserve the integrity of the host and to prevent development of disease. Vice versa, an impaired intestinal epithelial barrier function is a hallmark in the development and perpetuation of inflammatory bowel disease (IBD). Besides a multitude of genetic, molecular and cellular alterations predisposing for or driving barrier dysintegrity in IBD, the appearance of intestinal mucosal wounds is a characteristic event of intestinal inflammation apparently inducing breakdown of the intestinal epithelial barrier. Upon injury, the intestinal mucosa undergoes a wound healing process counteracting this breakdown, which is controlled by complex mechanisms such as epithelial restitution, proliferation and differentiation, but also immune cells like macrophages, granulocytes and lymphocytes. Consequently, the repair of mucosal wounds is dependent on a series of events including coordinated trafficking of immune cells to dedicated sites and complex interactions among the cellular players and other mediators involved. Therefore, a better understanding of the crosstalk between epithelial and immune cells as well as cell trafficking during intestinal wound repair is necessary for the development of improved future therapies. In this review, we summarize current concepts on intestinal mucosal wound healing introducing the main cellular mediators and their interplay as well as their trafficking characteristics, before finally discussing the clinical relevance and translational approaches to therapeutically target this process in a clinical setting.

scholarly journals Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhenping Wang ◽  
Yanhan Wang ◽  
Nicholas Bradbury ◽  
Carolina Gonzales Bravo ◽  
Bernd Schnabl ◽  
...  
Keyword(s):  
Immune Cells ◽  
Wound Repair ◽  
Molecular Mechanisms ◽  
Wound Closure ◽  
Skin Wound ◽  
Skin Cells ◽  
Transient Activation ◽  
Kit Receptor ◽  
Repair Mechanisms ◽  
Current Therapies

AbstractPoor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair, the cellular and molecular mechanisms of SCF in wound closure remain poorly understood. Here, we found that SCF expression in the epidermis is decreased in mouse models of delayed wound closure intended to mimic old age, obesity, and alcoholism. By using SCF conditionally knocked out mice, we demonstrated that keratinocytes’ autocrine production of SCF activates a transient c-kit receptor in keratinocytes. Transient activation of the c-kit receptor induces the expression of growth factors and chemokines to promote wound re-epithelialization by increasing migration of skin cells (keratinocytes and fibroblasts) and immune cells (neutrophils) to the wound bed 24–48 h post-wounding. Our results demonstrate that keratinocyte-produced SCF is essential to wound closure due to the increased recruitment of a unique combination of skin cells and immune cells in the early phase after wounding. This discovery is imperative for developing clinical strategies that might improve the body’s natural repair mechanisms for treating patients with wound-closure pathologies.

scholarly journals Mucosal Epithelial Jak Kinases in Health and Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Narendra Kumar ◽  
Longxiang Kuang ◽  
Ryan Villa ◽  
Priyam Kumar ◽  
Jayshree Mishra
Keyword(s):  
Immune Cells ◽  
Wound Repair ◽  
Epithelial Mesenchymal Transition ◽  
Transplant Rejection ◽  
Severe Combined Immunodeficiency ◽  
Organ Transplant ◽  
Therapeutic Interventions ◽  
Cell Physiology ◽  
Mesenchymal Transition ◽  
Epithelial Cancers

Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, viz., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.

scholarly journals Contribution of Wound-Associated Cells and Mediators in Orchestrating Gastrointestinal Mucosal Wound Repair

2019 ◽  
Vol 81 (1) ◽  
pp. 189-209 ◽  
Author(s):  
Miguel Quirós ◽  
Asma Nusrat
Keyword(s):  
Immune Cells ◽  
Stromal Cells ◽  
Wound Repair ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Mucosal Healing ◽  
Gastrointestinal Mucosa ◽  
Impaired Wound Healing ◽  
Epithelial Barrier Function ◽  
Mucosal Wound

The gastrointestinal mucosa, structurally formed by the epithelium and lamina propria, serves as a selective barrier that separates luminal contents from the underlying tissues. Gastrointestinal mucosal wound repair is orchestrated by a series of spatial and temporal events that involve the epithelium, recruited immune cells, resident stromal cells, and the microbiota present in the wound bed. Upon injury, repair of the gastrointestinal barrier is mediated by collective migration, proliferation, and subsequent differentiation of epithelial cells. Epithelial repair is intimately regulated by a number of wound-associated cells that include immune cells and stromal cells in addition to mediators released by luminal microbiota. The highly regulated interaction of these cell types is perturbed in chronic inflammatory diseases that are associated with impaired wound healing. An improved understanding of prorepair mechanisms in the gastrointestinal mucosa will aid in the development of novel therapeutics that promote mucosal healing and reestablish the critical epithelial barrier function.

scholarly journals Sterile Injury Repair and Adhesion Formation at Serosal Surfaces

2021 ◽  
Vol 12 ◽  
Author(s):  
Simone N. Zwicky ◽  
Deborah Stroka ◽  
Joel Zindel
Keyword(s):  
Wound Healing ◽  
Immune Cells ◽  
Wound Repair ◽  
Critical Role ◽  
Adhesion Formation ◽  
Clinical Importance ◽  
Body Cavity ◽  
Sterile Inflammation ◽  
Damage Recognition

Most multicellular organisms have a major body cavity containing vital organs. This cavity is lined by a mucosa-like serosal surface and filled with serous fluid which suspends many immune cells. Injuries affecting the major body cavity are potentially life-threatening. Here we summarize evidence that unique damage detection and repair mechanisms have evolved to ensure immediate and swift repair of injuries at serosal surfaces. Furthermore, thousands of patients undergo surgery within the abdominal and thoracic cavities each day. While these surgeries are potentially lifesaving, some patients will suffer complications due to inappropriate scar formation when wound healing at serosal surfaces defects. These scars called adhesions cause profound challenges for health care systems and patients. Therefore, reviewing the mechanisms of wound repair at serosal surfaces is of clinical importance. Serosal surfaces will be introduced with a short embryological and microanatomical perspective followed by a discussion of the mechanisms of damage recognition and initiation of sterile inflammation at serosal surfaces. Distinct immune cells populations are free floating within the coelomic (peritoneal) cavity and contribute towards damage recognition and initiation of wound repair. We will highlight the emerging role of resident cavity GATA6+ macrophages in repairing serosal injuries and compare serosal (mesothelial) injuries with injuries to the blood vessel walls. This allows to draw some parallels such as the critical role of the mesothelium in regulating fibrin deposition and how peritoneal macrophages can aggregate in a platelet-like fashion in response to sterile injury. Then, we discuss how serosal wound healing can go wrong, causing adhesions. The current pathogenetic understanding of and potential future therapeutic avenues against adhesions are discussed.

scholarly journals The Role of Immune Cells and Cytokines in Intestinal Wound Healing

2019 ◽  
Vol 20 (23) ◽  
pp. 6097 ◽  
Author(s):  
Xiang Xue ◽  
Daniel M. Falcon
Keyword(s):  
Wound Healing ◽  
Immune Cells ◽  
Wound Repair ◽  
Immune Cell ◽  
Cell Types ◽  
Repair Process ◽  
Interleukin 10 ◽  
Lymphoid Cells ◽  
Necrosis Factor Alpha ◽  
Interleukin 22

Intestinal wound healing is a complicated process that not only involves epithelial cells but also immune cells. In this brief review, we will focus on discussing the contribution and regulation of four major immune cell types (neutrophils, macrophages, regulatory T cells, and innate lymphoid cells) and four cytokines (interleukin-10, tumor necrosis factor alpha, interleukin-6, and interleukin-22) to the wound repair process in the gut. Better understanding of these immune factors will be important for developing novel targeted therapy.

scholarly journals Fibroblasts and Their Pathological Functions in the Fibrosis of Aortic Valve Sclerosis and Atherosclerosis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 472 ◽  
Author(s):  
Singh ◽  
Torzewski
Keyword(s):  
Extracellular Matrix ◽  
Aortic Valve ◽  
Immune Cells ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Interleukin 1 ◽  
Transforming Growth Factor Β1 ◽  
Aortic Valve Sclerosis ◽  
The Impact

Cardiovascular diseases, such as atherosclerosis and aortic valve sclerosis (AVS) are driven by inflammation induced by a variety of stimuli, including low-density lipoproteins (LDL), reactive oxygen species (ROS), infections, mechanical stress, and chemical insults. Fibrosis is the process of compensating for tissue injury caused by chronic inflammation. Fibrosis is initially beneficial and maintains extracellular homeostasis. However, in the case of AVS and atherosclerosis, persistently active resident fibroblasts, myofibroblasts, and smooth muscle cells (SMCs) perpetually remodel the extracellular matrix under the control of autocrine and paracrine signaling from the immune cells. Myofibroblasts also produce pro-fibrotic factors, such as transforming growth factor-β1 (TGF-β1), angiotensin II (Ang II), and interleukin-1 (IL-1), which allow them to assist in the activation and migration of resident immune cells. Post wound repair, these cells undergo apoptosis or become senescent; however, in the presence of unresolved inflammation and persistence signaling for myofibroblast activation, the tissue homeostasis is disturbed, leading to excessive extracellular matrix (ECM) secretion, disorganized ECM, and thickening of the affected tissue. Accumulating evidence suggests that diverse mechanisms drive fibrosis in cardiovascular pathologies, and it is crucial to understand the impact and contribution of the various mechanisms for the control of fibrosis before the onset of a severe pathological consequence.

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